The goal of any drug delivery system is to provide a therapeutic amount of drug to the proper site in the body to achieve and then maintain the desired drug concentration. The most convenient and commonly employed route of drug delivery has historically been by solid oral dosage forms, particularly tablets and capsules. However, conventional tablets and capsules are limited by their rigid dose content. Furthermore, difficulty swallowing tablets and capsules is a problem for many patients, and can lead to a variety of adverse events and patient noncompliance with treatment regimens.
Melatonin is an indole-derived hormone produced at night by the pineal gland, and it plays a major physiological role in the regulation of sleep. Melatonin is produced and secreted into the plasma in a circadian rhythm which parallels the sleep-wake cycle. Exogenous melatonin is often administered as a sleep-aid. Melatonin is also used to treat dependence on, tolerance of, or addiction to a benzodiazepine, as described in U.S. Pat. No. 6,469,044, the disclosure of which is incorporated herein by reference in its entirety. Treatment with melatonin has been shown to produce positive effects on sleep induction, sleep quality, and most importantly, day-time-functioning as well as quality of life. Melatonin use is not associated with development of dependency.
Melatonin is available in several solid oral dosage forms, particularly tablets and capsules. Existing melatonin oral dosage forms include immediate-release dosage forms, useful for treating delayed sleep onset, and prolonged release forms, useful for sleep maintenance. Oral absorption of melatonin is rapid and peak plasma levels are achieved 20 to 60 min following ingestion.
Existing melatonin products suffer from disadvantages including poor patient compliance issues due to difficulty in swallowing tablets, e.g., prolonged-release Circadin® tablets, which are about 8.1 mm in diameter and 3-5 mm thick. Due to these difficulties, some patients break, crush, or chew the prolonged-release Circadin® tablets, which results in loss of its prolonged-release profile. As such, when Circadin® tablets are broken, crushed or chewed, they exhibit a release profile that is close to immediate-release melatonin.
There exists a need in the art for improved drug delivery systems for use in patient populations having an inability to swallow tablets and capsules, e.g., pediatric and geriatric populations. Specifically, there exists a need in the art for novel mini-tablet formulations. Even more specifically, there exists a need in the art for novel melatonin mini-tablet formulations having precise pharmacologic and pharmacokinetic properties.